Today is Sunday, Jul. 21, 2019

Systems Biology and Physiology Graduate Program

Current Students  |  Ted Hong

My thesis project is about the roles of viral TF in human diseases, mainly focusing on the roles of EBNA2 TF from Epstein-Barr virus in autoimmune-associated gene regulation, since EBNA2 was known to regulate human gene expression in B cells. To test the hypothesis that EBNA2 alters host gene expression levels by rearranging the chromatin landscape, we first infected human B cells with the EBNA2+ EBV strain and also the EBNA2- EBV strain. We then identified EBNA2-dependent differentially expressed genes (DEGs) by comparing EBNA2+, EBNA2- infected and also uninfected RNA-Seq data, which resulted in 421 EBNA2 dependent DEGs. Using the RELI algorithm (Regulatory Element Locus Intersection) that we published previously, we found significant intersection between EBNA2-dependent DEGs and autoimmune-associated SNPs. We also performed EBNA2 ChIP-seq, which was also significantly intersected with EBNA2-dependant DEGs and autoimmune-SNPs. We also found allele-dependent binding of eight transcription factors including CTCF, RAD21, SMC3 and EBNA2 to five autoimmune-associated SNPs in five different loci were in the same topologically associating domain (TAD) as allele-dependent expression of 6 EBNA2-DEGs, implying the roles of genetic variation in regulating TF binding and EBNA2-dependent gene expression. We then performed ATAC-seq with EBNA2+ EBNA-, uninfected condition to see if EBNA2 can alter chromatin environment and identified about 500 EBNA2-dependent open chromatin regions. By running homer and RELI, we found enrichment of CTCF, RAD21, and YY1 (looping factors) only in the EBNA2+ ATAC-seq condition. Allelic binding of CTCF and RAD21 to vitiligo SNPs were also found within EBNA2-dependent regions, suggesting disease-relevant roles of EBNA2 in modifying chromatin structures.

Taken together, our results reveal the role of EBNA2 in extensive rewiring of the gene regulatory network of the host partially through the rearranging of the chromatin landscape.
Ted Hong

Year in Program: 5th

Hometown: Seoul, South Korea

Mentor: Dr. Weirauch


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